mAbs最新文献

{"title":"Engineered ipilimumab variants that bind human and mouse CTLA-4.","authors":"Brett Robison, S J Diong, Anusha Kumar, Thomas M Moon, Olin Chang, Bryant Chau, Christine Bee, Ishita Barman, Arvind Rajpal, Alan J Korman, Sean West, Pavel Strop, Peter S Lee","doi":"10.1080/19420862.2025.2451296","DOIUrl":"10.1080/19420862.2025.2451296","url":null,"abstract":"<p><p>Testing of candidate monoclonal antibody therapeutics in preclinical models is an essential step in drug development. Identification of antibody therapeutic candidates that bind their human targets and cross-react to mouse orthologs is often challenging, especially for targets with low sequence homology. In such cases, surrogate antibodies that bind mouse orthologs must be used. The antibody 9D9, which binds mouse CTLA-4, is a commonly used surrogate for CTLA-4 checkpoint blockade studies in mouse cancer models. In this work, we reveal that 9D9 has significant biophysical dissimilarities to therapeutic CTLA-4 antibodies. The 9D9-mCTLA4 complex crystal structure was determined and shows that the surrogate antibody binds an epitope distinct from ipilimumab and tremelimumab. In addition, while ipilimumab has pH-independent binding to hCTLA-4, 9D9 loses binding to mCTLA-4 at physiologically relevant acidic pH ranges. We used phage and yeast display to engineer ipilimumab to bind mouse CTLA-4 with single-digit nM affinity from an initial state with no apparent binding. The engineered variants showed pH-independent and cross-reactive binding to both mouse and human CTLA-4. Crystal structures of a variant in complex with both mouse and human CTLA-4 confirmed that it targets an equivalent epitope as ipilimumab. These cross-reactive ipilimumab variants may facilitate improved translatability and future mechanism-of-action studies for anti-CTLA-4 targeting in murine models.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2451296"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The nonglycosylated variant in therapeutic monoclonal antibodies preferentially forms large aggregates under typical thermal stresses used in forced degradation studies.","authors":"Gao-Yuan Liu, Jenny Kim Kim, Shuli Tang, Yuetian Yan, Mandi Hopkins, Dalia Laredo, Teng-Chieh Yang, James Mutino, Douglas E Kamen, Kenneth S Graham, Mohammed Shameem, Shunhai Wang, Ning Li","doi":"10.1080/19420862.2025.2543768","DOIUrl":"10.1080/19420862.2025.2543768","url":null,"abstract":"<p><p>Monoclonal antibodies (mAbs) feature a conserved N-linked glycosylation site in the CH2 domain, which exhibits heterogeneities in both occupancy and glycan structures. Previous studies have suggested that the unoccupied (nonglycosylated) variant exhibits decreased thermal stability, potentially impacting the overall stability of mAb products. This hypothesis, however, has remained largely unconfirmed, due to the low abundance of nonglycosylated variants in typical mAb products and the lack of effective analytical tools for detailed characterization of large aggregates with glycoform-specific information. Here, we used a postcolumn denaturation-assisted size exclusion chromatography mass spectrometry technique (SEC-PCD-MS) to reevaluate the effects of the nonglycosylated mAb variant on the thermal stability of mAb drugs during forced degradation studies. Our findings confirmed the compromised thermal stability of the nonglycosylated variant and its increased propensity to form large aggregates at elevated temperatures relevant to mAb-forced degradation studies. We also showed that this thermal stress-induced, nonglycosylation-mediated aggregation pathway could be widely observed in a diverse group of mAb molecules with varying properties. This study offers valuable insights into the rationale of selecting the appropriate temperature for mAb-forced degradation studies and highlights key considerations for data interpretation.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2543768"},"PeriodicalIF":7.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144817073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel throughput assay to assess molecular hydrophobicity during early biotherapeutic developability assessments.","authors":"Maureen Crames, Mya Davis, Michael S Marlow","doi":"10.1080/19420862.2025.2562999","DOIUrl":"10.1080/19420862.2025.2562999","url":null,"abstract":"<p><p>Developability studies provide essential data to identify monoclonal antibodies (mAbs) with optimal drug-like properties, which are indicative of a molecule's suitability for large-scale manufacturing, long-term storage, and ease of administration. Hydrophobicity is a critical molecular attribute that affects solubility, aggregation, and stability at high protein concentrations and is routinely assessed in these studies. Although traditional analytical hydrophobic interaction chromatography (aHIC) is considered the benchmark for measuring hydrophobicity, its application in early developability studies is limited because the process requires serial sample injections, which is time-intensive and impractical for the evaluation of hundreds of molecules. To overcome this limitation, we developed an alternative aHIC method that uses a plate-based assay format, enabling rapid screening of large sample sets. Compatible with automation platforms, this surrogate aHIC method demonstrates excellent accuracy in distinguishing between low- and high-risk molecules, proving to be an efficient tool for preliminary developability assessments. This innovative assay provides a robust, timesaving, and sample-efficient means of evaluating hydrophobicity that readily supports early phase biotherapeutic antibody discovery through selection of mAbs with favorable drug-like properties. Furthermore, the potential for adaptation of this method to various molecular formats suggests its broad applicability in biotherapeutic discovery.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2562999"},"PeriodicalIF":7.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving dual targeting selectivity in T-cell engagers via synapse-gated and affinity-tuned trispecific antibody design.","authors":"Peng Zhao, John Schardt, Chi-I Chiang, Pooja Shah, Gee Sung Eun, Jan Martinek, Matthew Cyr, Yoshimi Johnson, Bismark Amofah, Xiaoying Ye, Samuel Edwards, Xiaoru Chen, Mark Penney, Wenhai Liu, Chunning Yang, Keith Rickert, Amber Lee, Sterling Payne, Hanzhi Zhang, Garrett Kelly, Chunlei Wang, Allison Gerber, Kathy Mulgrew, Rajat Varma, Jonathan Boyd, Xiuling Li, John D Bagert, Even Walseng, Yariv Mazor","doi":"10.1080/19420862.2025.2570748","DOIUrl":"https://doi.org/10.1080/19420862.2025.2570748","url":null,"abstract":"<p><p>T-cell engagers (TCEs) represent a powerful drug modality for redirecting a patient's own T cells to recognize and eradicate cancer cells. Although TCEs have been effective in treating hematological cancers, their broad application for solid tumors has been more challenging due to the absence of tumor-specific antigens. This often leads to on-target, off-tumor toxicities and a low therapeutic index (TI). Strategies for dual-antigen targeting of double-positive cancer cells over single-positive normal tissue may improve the TI of TCEs. In this study, we report the development and characterization of a conditional dual tumor-associated antigen (TAA)-targeting trispecific antibody (TriMab) TCE composed of a non-active anchoring arm (<i>i.e</i>. anti-TAA1), deficient in mediating an active immunological synapse, and an affinity-tuned active arm (<i>i.e</i>. anti-TAA2), paired with an anti-CD3 domain to drive AND-gated targeting and elimination of dual-TAA tumors while sparing single-TAA healthy cells. Using an anti-receptor tyrosine kinase-like orphan receptor 1 (ROR1) mAb as a proof-of-concept anchoring arm and an array of affinity-modulated variants of the anti-epidermal growth factor receptor (EGFR) GA201 mAb as active arms, we show <i>in vitro</i> conditional engagement and elimination of double-positive human NCI-H358 non-small cell lung cancer cells over single-positive, non-target NCI-H358.ROR1.KO cells by affinity-modulated TriMab TCEs. <i>In vivo</i>, the TriMab TCE exhibits selective targeting and eradication of ROR1/EGFR double-positive tumors in a mouse xenograft model. We further demonstrate the generality of the anchoring arm in TriMab using anti-HER2 mAbs targeting different binding epitopes and discuss the interplay of factors regulating immunological synapse formation. Lastly, we demonstrate that the TriMab modality exhibits a favorable developability profile and mAb-like pharmacokinetic properties in human neonatal Fc receptor transgenic mice. Overall, this work presents a generalizable approach to utilizing the TriMab modality by leveraging avidity effects and molecular geometry to achieve conditional AND-gated dual TAA-targeting with a significantly improved TI.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2570748"},"PeriodicalIF":7.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing large-molecule discovery with a unified digital platform for data analysis and workflow management.","authors":"Eriberto Natali, Jana Hersch, Christoph Freiberg, Stephan Steigele","doi":"10.1080/19420862.2025.2555346","DOIUrl":"10.1080/19420862.2025.2555346","url":null,"abstract":"<p><p>The repertoire of large-molecule treatments continues to expand, resulting in diverse discovery and development workflows. This diversity yields a proliferation of software solutions and procedures for molecule registration, material tracking, experiment planning, data analytics, quality control, data sharing, and decision-making. Contrasting with this manual, labor intensive, and error-prone approach, we introduce the concept of a transformative solution: an integrated platform that translates this complexity into a harmonized, open architecture encompassing all workflows and hardware systems, covering the discovery process up to developability assessment. The benefits and complexities of such a platform are evident in examples spanning different use cases and maturity levels, such as developing multi-specific antibodies and antibody-drug conjugates using shared workflows or incorporating artificial intelligence for predictive and generative tasks. This review outlines state-of-the-art concepts behind a digital platform for automating and streamlining the discovery of new large-molecule treatments.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2555346"},"PeriodicalIF":7.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nipocalimab, an immunoselective FcRn blocker that lowers IgG and has unique molecular properties.","authors":"Nilufer P Seth, Rui Xu, Matthew DuPrie, Amit Choudhury, Samuel Sihapong, Steven Tyler, James Meador, William Avery, Edward Cochran, Thomas Daly, Julia Brown, Laura Rutitzky, Lynn Markowitz, Sujatha Kumar, Traymon Beavers, Sayak Bhattacharya, Hsin Chen, Viraj Parge, Karen Price, Yang Wang, Siddharth Sukumaran, Yvonne Pao, Katie Abouzahr, Fiona Elwood, Jay Duffner, Sucharita Roy, Pushpa Narayanaswami, Jonathan J Hubbard, Leona E Ling","doi":"10.1080/19420862.2025.2461191","DOIUrl":"10.1080/19420862.2025.2461191","url":null,"abstract":"<p><p>Nipocalimab is a human immunoglobulin G (IgG)1 monoclonal antibody that binds to the neonatal Fc receptor (FcRn) with high specificity and high affinity at both neutral (extracellular) and acidic (intracellular) pH, resulting in the reduction of circulating IgG levels, including those of pathogenic IgG antibodies. Here, we present the molecular, cellular, and nonclinical characteristics of nipocalimab that support the reported clinical pharmacology and potential clinical application in IgG-driven, autoantibody- and alloantibody-mediated diseases. The crystal structure of the nipocalimab antigen binding fragment (Fab)/FcRn complex reveals its binding to a unique epitope on the IgG binding site of FcRn that supports the observed pH-independent high-binding affinity to FcRn. Cell-based and in vivo studies demonstrate concentration/dose- and time-dependent FcRn occupancy and IgG reduction. Nipocalimab selectively reduces circulating IgG levels without detectable effects on other adaptive and innate immune functions. In vitro experiments and in vivo studies in mice and cynomolgus monkeys generated data that align with observations from clinical studies of nipocalimab in IgG autoantibody- and alloantibody-mediated diseases.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2461191"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Folate receptor alpha for cancer therapy: an antibody and antibody-drug conjugate target coming of age.","authors":"Yi Liu, Xinyi Chen, Theodore Evan, Benjamina Esapa, Alicia Chenoweth, Anthony Cheung, Sophia N Karagiannis","doi":"10.1080/19420862.2025.2470309","DOIUrl":"10.1080/19420862.2025.2470309","url":null,"abstract":"<p><p>Folate receptor alpha (FRα) has long been the focus of therapeutics development in oncology across several solid tumors, notably ovarian, lung, and subsets of breast cancers. Its multiple roles in cellular metabolism and carcinogenesis and tumor-specific overexpression relative to normal tissues render FRα an attractive target for biological therapies. Here we review the biological significance, expression distribution, and characteristics of FRα as a highly promising and now established therapy target. We discuss the ongoing development of FRα-targeting antibodies and antibody-drug conjugates (ADCs), the first of which has been approved for the treatment of ovarian cancer, providing the impetus for heightened research and therapy development. Novel insights into the tumor microenvironment, advances in antibody engineering to enhance immune-mediated effects, the emergence of ADCs, and several studies of anti-FRα agents combined with chemotherapy, targeted and immune therapy are offering new perspectives and treatment possibilities. Hence, we highlight key translational research and discuss several preclinical studies and clinical trials of interest, with an emphasis on agents and therapy combinations with potential to change future clinical practice.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2470309"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanoscale warriors against viral invaders: a comprehensive review of Nanobodies as potential antiviral therapeutics.","authors":"Vaishali Verma, Nimisha Sinha, Abhavya Raja","doi":"10.1080/19420862.2025.2486390","DOIUrl":"10.1080/19420862.2025.2486390","url":null,"abstract":"<p><p>Viral infections remain a significant global health threat, with emerging and reemerging viruses causing epidemics and pandemics. Despite advancements in antiviral therapies, the development of effective treatments is often hindered by challenges, such as viral resistance and the emergence of new strains. In this context, the development of novel therapeutic modalities is essential to combat notorious viruses. While traditional monoclonal antibodies are widely used for the treatment of several diseases, nanobodies derived from heavy chain-only antibodies have emerged as promising \"nanoscale warriors\" against viral infections. Nanobodies possess unique structural properties that enhance their ability to recognize diverse epitopes. Their small size also imparts properties, such as improved bioavailability, solubility, stability, and proteolytic resistance, making them an ideal class of therapeutics for viral infections. In this review, we discuss the role of nanobodies as antivirals against various viruses. Techniques used for developing nanobodies, delivery strategies are covered, and the challenges and opportunities associated with their use as antiviral therapies are discussed. We also offer insights into the future of nanobody-based antiviral research to support the development of new strategies for managing viral infections.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2486390"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11988260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of potent humanized TNFα inhibitory nanobodies for therapeutic applications in TNFα-mediated diseases.","authors":"Tao Yin, Aubin Ramon, Matthew Greenig, Pietro Sormanni, Luciano D'Adamio","doi":"10.1080/19420862.2025.2498164","DOIUrl":"https://doi.org/10.1080/19420862.2025.2498164","url":null,"abstract":"<p><p>Tumor necrosis factor-alpha (TNFα) is a key pro-inflammatory cytokine implicated in the pathogenesis of numerous inflammatory and autoimmune diseases, including rheumatoid arthritis, inflammatory bowel disease, and neurodegenerative disorders such as Alzheimer's disease. Effective inhibition of TNFα is essential for mitigating disease progression and improving patient outcomes. In this study, we present the development and comprehensive characterization of potent humanized TNFα inhibitory nanobodies (TNFI-Nbs) derived from camelid single-domain antibodies. In silico analysis of the original camelid nanobodies revealed low immunogenicity, which was further reduced through machine learning-guided humanization and developability optimization. The two humanized TNFI-Nb variants we developed demonstrated high anti-TNFα activity, achieving IC₅₀ values in the picomolar range. Binding assays confirmed their high affinity for TNFα, underscoring robust neutralization capabilities. These TNFI-Nbs present valid alternatives to conventional monoclonal antibodies currently used in human therapy, offering potential advantages in potency, specificity, and reduced immunogenicity. Our findings establish a solid foundation for further preclinical development and clinical translation of TNFα-targeted nanobody therapies in TNFα-mediated diseases.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2498164"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The physiological limits of bispecific monoclonal antibody tissue targeting specificity.","authors":"Armin Sepp, Felix Stader, Abdallah Derbalah, Cong Liu, Adriana Zyla, Iain Gardner, Masoud Jamei","doi":"10.1080/19420862.2025.2492236","DOIUrl":"https://doi.org/10.1080/19420862.2025.2492236","url":null,"abstract":"<p><p>Bispecific monoclonal antibodies (bsmAbs) are expected to provide targeted drug delivery that overcomes the dose-limiting toxicities often accompanying antibody-drug conjugates (ADC) in clinical practice. Much attention has been paid in the past to target selection, mAb affinities and the payload linker design, but challenges remain. Here, we demonstrate, by physiologically based pharmacokinetic (PBPK) <i>in silico</i> modeling and simulation, that the tissue-targeting accuracy of mono- and bispecific antibody therapeutics is substantially limited by normal physiological characteristics like organ volumes, blood flow rates, lymphatic circulation, and rates of extravasation. Only a small fraction of blood flows through solid tumor, where the diffusion-driven extravasation is relatively slow compared with many other organs. EGFR and HER2 are used as model antigens based on their experimentally measured tissue and tumor expression levels, but the approach is generic and can account for the cellular expression variation of targets. The model confirms experimental observations that only about 0.1-1% of the dosed mAb is likely to reach the tumor, while the rest ends up in healthy tissues due to target-mediated internalization and nonspecific uptake. The model suggests that the dual-positive tumor cell targeting specificity with bispecific antibodies is likely to be higher at lower drug concentrations and doses. However, this can be offset by elevated drug exposure in more accessible healthy tissues, primarily endothelium. The balance of exposure can be shifted toward tumor cells by using higher doses, albeit at the expense of more extensive target engagement elsewhere in the body, suggesting the need to adapt the toxicity of the payload if ADCs are considered. We suggest that PBPK modeling can guide and support biologics and bsmAb development, from target evaluation and drug optimization to therapeutic dose selection.</p>","PeriodicalId":18206,"journal":{"name":"mAbs","volume":"17 1","pages":"2492236"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}